As a method of obtaining a volume fraction of cells in a cell suspension, a technique of using low-frequency electric conductivity (frequency of 100 kHz or less) of the suspension and low-frequency electric conductivity (frequency of 100 kHz or less) of a solvent containing no cell is known (NPL 1). In a suspension in which, for example, spherical cells are thinly dispersed, the volume fraction of cells can be obtained as Formula (1) shown below:
                    [                  Math          .                                          ⁢          1                ]                                                            ϕ        =                  2          ⁢                                                    κ                a                            -                              κ                b                                                                    2                ⁢                                  κ                  a                                            +                              κ                b                                                                        (        1        )            
ϕ: Volume fraction
κa: Electric conductivity of the solvent
κb: Electric conductivity of the suspension
If the shape of suspended cells is not spherical, on the other hand, it is also necessary to consider the shape of cells and in a suspension in which, for example, cells in a spheroidal shape are thinly dispersed, the volume fraction of cells can be obtained as Formula (2) shown below:
                    [                  Math          .                                          ⁢          2                ]                                                            ϕ        =                  9          ⁢                                                    (                                                      1                                          1                      -                      Lz                                                        +                                      2                                          1                      -                                              L                        ⁡                                                  (                                                      x                            =                            y                                                    )                                                                                                                    )                                            -                1                                      ·                                                            κ                  a                                -                                  κ                  b                                                                              2                  ⁢                                      κ                    a                                                  +                                  κ                  b                                                                                        (        2        )            
ϕ: Volume fraction
κa: Electric conductivity of the solvent
κb: Electric conductivity of the suspension
Lx, Ly, Lz: Parameters related to the shape or the like of the spheroid
For a concentrated suspension in which the cell density is high and which is not handled as a thinly dispersed system, it is necessary to use another formula that takes an interaction between cells into consideration.
However, these conventional methods need to use electric conductivity of a solvent that does not contain cells and it is difficult to obtain the volume fraction of cells from data of a suspension only. In addition, cells need to be dispersed in the solvent without being agglutinated. Thus, in the case of, for example, blood containing plasma components, rouleaux and agglutination of erythrocytes are formed and therefore, it is difficult to determine the volume fraction of erythrocytes and so on by the conventional method. In addition, the degree of rouleaux or agglutination changes in various ways depending on the flow of blood or the time after leaving at rest and therefore, it is difficult to determine a formula that factors in the degree of rouleaux or agglutination and currently, such a formula is not known.
As the common blood coagulation test, blood coagulation tests including the prothrombin time (PT) and the activated partial thromboplastin time (APTT) are known. These are methods that analyze proteins contained in plasma obtained by centrifuging a blood sample and involved in a coagulation reaction. It has been considered that this field is technically established and needs in medical sites are almost met.
However, in order to respond to needs of wanting to appropriately and handily test comprehensive pathologic conditions of coagulation of a patient in the perioperative (acute phase) treatment in which promptness is demanded, the aforementioned methods are insufficient. More specifically, for example, in a major operation such as a heart operation involving extracorporeal circulation by an artificial heart-lung machine, treatment of major physical trauma, or a liver transplantation operation, not only surgical bleeding, but also bleeding caused by anomalous coagulation may continue. Nevertheless, cell components such as platelets and erythrocytes playing an important role in the coagulation reaction in the body are removed by centrifugation in the conventional coagulation test and thus, test results are frequently at variance with actual clinical pathologic conditions.
In addition, coagulating pathologic conditions of a patient may greatly vary throughout a perioperative period and may often change from a bleeding tendency to a thrombus tendency, but PT and APTT are tests of the bleeding tendency and a sensitive test method of the thrombus tendency is not yet been established.
As a comprehensive coagulation test for an acute period, thromboelastometry that mechanically measures viscoelasticity changes accompanying the blood coagulation process has been commercially introduced by European and American companies as TEG (registered trademark) or ROTEM (registered trademark). However, (1) measurements are not automated and measurement results depend on the procedure of the measuring person, (2) measurements are likely to be subject to vibration, (3) the quality control (QC) procedure is complex and the reagent for QC is expensive, and (4) a skilled labor is necessary for interpretation of an output signal (thromboelastogram) are considered to be main reasons that widespread use thereof is not achieved. Thus, for patients who do not need blood transfusion if a comprehensive coagulation test is performed, blood preparations are currently used empirically as a means of prevention, which increases not only risks of infectious disease, but also waste of blood preparations and medical expenses.
In recent years, technologies that handily and correctly evaluate the degree of coagulation of blood are under development. For example, Patent Literature 1 discloses a technology that acquires information about blood coagulation from the dielectric constant of blood and “A blood coagulation system analysis device including: a pair of electrodes; an applying unit that applies an alternating voltage to the pair of electrodes at predetermined intervals; a measuring unit that measures a dielectric constant of blood disposed between the pair of electrodes; and an analysis unit that analyzes a degree of working of a blood coagulation system using the dielectric constant of the blood measured at the time intervals after anticoagulant action working on the blood is released” is described.
As a blood specimen for this method, blood collected from a vein while using citric acid as an anticoagulant is generally used. An anticoagulation treatment releasing agent such as a calcium chloride solution is used immediately before the measurement is started to release the anticoagulation action and then, measurements are made after a blood coagulation reaction is in progress.